Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways

Rao, Xiaoquan; Zhao, Shi; Braunstein, Zachary; Mao, Hong; Razavi, Michael; Duan, Lihua; Wei, Yingying; Toomey, Amelia C.; Rajagopalan, Sanjay; Zhong, Jixin

We acknowledge a number of important limitations in this study. Importantly, we have not demonstrated a link between mediators of triglycerides such as post-prandial remnants. Remnant lipoproteins are markedly increased in diabetic dyslipidemia and may represent a fraction that could potentially participate in linking disordered lipid metabolism in the post-prandial state with abnormalities in glucose metabolism. In addition, we acknowledged that the DPP4 expression in human monocytes was not examined in a large sample of patients. However, one critical finding in our human study that DPP4 is increased in obesity and atherosclerosis is supported by other reports with a larger population size [9, 24] . We have also not provided additional mechanisms that link changes in TLR4 expression with downstream activation of TRIF and further kinase pathways that may function upstream of DPP4. In conclusion we demonstrate a role for oxidized lipids mediated up-regulation of DPP4 in atherosclerosis via TLR4/TRIF and CD36 dependent pathways. Our data provides a link between disordered lipid metabolism in atherosclerosis and impaired glucose intolerance through upregulation of DPP4.